Abstract
Major depression disorder (MDD) has become a common life-threatening disorder. Despite the number of studies and the introduced antidepressants, MDD remains a major global health issue. Carthamus tinctorius (safflower) is traditionally used for food and medical purposes. This study investigated the chemical profile and the antidepressant-like effect of the Carthamus tincto-rius hot water extract in male mice and its mechanism using a transcriptomic analysis. The antidepressant effect of hot water extract (50 mg/kg and 150 mg/kg) was investigated in mice versus the untreated group (saline) and positive control group (fluoxetine 10 mg/kg). Hippocampus transcriptome changes were investigated to understand the Carthamus tinctorius mechanism of action. The GCMS analysis of Carthamus tinctorius showed that hot water extract yielded the highest amount of oleamide as the most active ingredient. Neuro-behavioral tests demonstrated that the safflower treatment significantly reduced immobility time in TST and FST and improved performance in the YMSAT compared to the control group. RNA-seq analysis revealed a significant differential gene expression pattern in several genes such as Ube2j2, Ncor1, Tuba1c, Grik1, Msmo1, and Casp9 related to MDD regulation in 50 mg/kg safflower treatment as compared to untreated and fluoxetine-treated groups. Our findings demonstrated the antidepressant-like effect of safflower hot water extract and its bioactive ingredient oleamide on mice, validated by a significantly shortened immobility time in TST and FST and an increase in the percentage of spontaneous alternation.